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Join A Prostate Cancer Imaging Clinical Trial

Dr. Peter Choyke, Director of the Molecular Imaging Program at the National Institutes of Health’s National Cancer Institute, is keenly interested in translating molecular imaging methods like MRI and PET into practice.

Prostatepedia spoke with him about his clinical trial on 18F-DCFPyL PET/CT imaging in high-risk prostate cancer.

Why did you become a doctor?

Dr. Peter Choyke: I was always interested in science. I came from a family of scientists. It just seemed that medical problems were the kind of problems that I needed to do work on. A lot of the problems in physics and chemistry had been solved, but in biology and medicine we really needed a lot more effort. I wanted to devote my life to that.

Can you explain the thinking behind your clinical trial on 18F-DCFPyL PET/CT imaging in high-risk prostate cancer?

Dr. Choyke: Prostate cancer imaging has been very limited. We’ve only had access to CT and bone scans, both of which had limited sensitivity for picking up prostate cancer. In the beginning of the 2000s, a number of new PET agents—or Positronemission tomography labeled agents—emerged. We started looking at them as they became available. They showed better and better sensitivity and specificity.

About three or four years ago, we accessed a first generation PSMA-targeted PET agent named F-18 DCFBC in collaboration with the person who invented this whole field, Dr. Martin Pomper at Johns Hopkins University.

We formed a collaboration and scanned 135 patients in an earlier protocol. We showed that even though this was a first generation PSMA agent, it was really promising and had much better sensitivity and specificity for prostate cancer than any other agent we had ever looked at.

Then Dr. Pomper, who is partly an imaging specialist and partly a chemist, further developed the compound into F-18 DCFPYL. This is the agent we’re now using in this trial.

F-18 DCFPYL has probably 10 times better sensitivity than the first-generation agent because of the higher affinity of the agent for PSMA and because of lower background. We started using that in the end of the summer of 2017 in a trial looking at high-risk primary cancer and recurrent disease.

If a man enrolls in this trial, what can he expect to happen from beginning to end?

Dr. Choyke: First of all, it’s important to talk about who qualifies for the trial. We have two arms.

In one arm, we’ll have men with high risk cancers, meaning they’re at high risk for metastatic disease or spread outside the prostate. Such men would come to our center and get the scan. They’d also get an MRI of their prostate, because we always correlate the findings of the DCFPyL scan with MRI to anatomically locate where the uptake is occurring. The anatomy is very complex in the low pelvis.

With the MRI in hand, the patient would get an injection of a small amount of radioactivity in the form of this F-18 DCFPyL. About an hour later, they go onto the scanner and simply lie flat for about 20 to 30 minutes until the entire body is scanned from head to toe. Then we’ll report the findings back to his physician.

Part of the reason why this is a research study is that we try very hard to correlate the findings that we see with biopsy specimens. This is still a research agent. We don’t know for sure that the areas of uptake are actually cancer. We can only confirm that with biopsy. We insist that patients undergo biopsy of PSMA-positive lesions as seen on the scan.

We say insist, though of course it may not be medically safe for some people to undergo a biopsy. It may not be feasible. There are exceptions. It’s not an absolute rule. We certainly want to get as much histologic correlation as possible. Otherwise, we could end up in a situation where we think we’re seeing disease, but we are in fact not. That would be very misleading and could possibly cause more harm than good. It’s very important at this stage of development to get as much information as possible.

In the second arm of this trial, we are scanning patients who have already undergone radical prostatectomy or radiation therapy and who now have a rising PSA, which indicates recurrent disease. We would do the scan in the same way as in the first arm with correlation of the MRI. Again, we’re trying to get as much histologic confirmation as possible.

Join us to read the rest of Dr. Choyke’s comments about his clinical trial.

 

 


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3 or Fewer Prostate Cancer Mets

Dr. Piet Ost is a radiation oncologist at Ghent University in Belgium. His work focuses on post-surgery radiation therapy and metastasis-directed therapy for oligometastatic prostate cancer, or a cancer recurrence with three or fewer metastases.

Prostatepedia spoke with him about treating men with so few metastases after treatment.

Can you define oligometastatic prostate cancer?

Dr. Ost: First of all, if your doctor talks about oligometastatic disease, I think it’s very important to ask them what they mean by that? When we look through literature, there are several definitions used.

Some people use oligometastatic while others use oligorecurrence, synchronous metastases, or low volume metastases. Many of these probably mean the same, but there is no uniform definition.

In 1995, Hellman and Weichselbaum first defined oligometastases as metastases limited in number and location. These tumors have not developed the full capacity for metastatic growth. It could be an issue with the metastases—or the seed—or it could be an issue with the soil—the environment in which the metastases started to grow. That’s the biological definition.

This is not very useful as a clinician. What is limited? Is that a certain number? If you look through literature, many clinicians define it as up to three metastatic lesions with no more than two different organs involved. That is probably the most used definition, but there are alternatives. Some say that it’s only one metastasis while others say it’s as many as five or even 10 in case of brain metastases. Some say there has to be a certain amount of time between primary diagnosis and the occurrence of metastasis.

There’s a lot of confusion throughout the literature. If you read an article, you have to look at their definition. When doctors talk to each other, and when patients talk to each other, they all use the word oligometastatic, but it might be that they’re talking about a different disease.

Is there any sort of restriction on where those metastases are located—for example, in only the pelvic area?

Dr. Ost: At this time, I don’t think so. It’s a biological phenotype. We care less where the metastasis occurs. For example, we have had patients with unique lung mets at the time of recurrence where we remove those lung mets, and then these patients remain disease-free for many months or even years.

Normally, when you have a patient with lung mets, those are visceral mets, and their prognosis is supposed to be very poor no matter what. There appears to be a subset of patients with a limited number of metastases, even visceral metastases, who still benefit from removing or irradiating the metastases. We have several of those cases documented already. It’s not about the location. It’s something about the biology, and that is the big problem at this time.

Currently, when we propose a certain oligometastatic or metastasis directed therapy to a patient, we don’t know if the metastases we see and treat are the only ones there, or if three months after we remove or eradiate them, there will be 20 new metastases. We don’t know that at the start. This shows us that imaging is still far from perfect and sometimes we only see the tip of the iceberg.

When we look at the distribution or pattern of metastases in recurrent prostate cancer with Choline PET/CT and PSMA PET/CT imaging, we see that, after receiving prior prostate cancer treatment, the majority of patients relapse first in the lymph nodes.

That is mainly in the pelvic lymph nodes. If we look at all the patients that we screen for now, 70% have nodal recurrences, 25% have bone metastases, and 5% have visceral mets. If we look at all of those recurrences, two thirds of those relapses are what we call oligometastatic, meaning up to three metastatic spots. We don’t believe that there is a true limitation on the organs. How it evolves is actually a fingerprint of the disease.

When you start, you don’t know whether it’s a true oligomet. We cannot predict at this time how the disease will evolve.

How do you normally treat oligomets? With radiation or surgery? How do you decide which is most appropriate?

Dr. Ost: We still counsel our patients on the standard options. For patients with upfront metastatic disease, the landscape has changed dramatically where we now introduce Androgen Deprivation Therapy (ADT) plus Taxotere (docetaxel) or ADT plus Zytiga (abiraterone) as a standard of care.

We still do not know if these options are helpful in treating the primary tumor and its mets with metastatic-directed therapy. In situations with upfront oligometastatic disease, we counsel our patients that the standard of care is systemic drugs while the addition of any metastatic-directed therapy is one big question mark. We do not advise it outside clinical trial.

The situation is a bit different in the recurrent setting. In the recurrent setting, there’s a gray zone. For example, the older data said that starting ADT for a PSA relapse following primary therapies—just starting ADT—is not advised; it’s better to wait and see and do a delayed ADT at the time of symptomatic progression.

Now with the very sensitive imaging, we see mets earlier at PSA relapse. What should we do with these? Do we still say the standard of care is wait and see, ADT, or something else? Because new imaging created this gray zone, all of a sudden we saw a boom in these oligometastatic patients, so we decided to do a clinical trial in this setting.

In our paper published in The Journal of Clinical Oncology (JCO), we randomized our patients to wait and see. One group had surveillance while starting ADT, and the other group had surgery or radiotherapy to the mets followed by surveillance. In that study, we found that surgery or radiotherapy is better at postponing further progression to polymetastatic disease rather than just observing patients.

We have an alternative now in counseling patients: metastaticdirected therapy with either surgery or radiotherapy. We know that it’s very safe, because we did not see any grade 2 or higher toxicity, which is a positive thing to tell men with prostate cancer. We can offer you something without a whole lot of toxicity. We still have to tell you this was a Phase II trial. The endpoint was time to progression.

I’m still not sure that giving metastatic-directed therapy will change your disease in the long run, that it will make you live any longer compared with immediate ADT or surveillance. It’s still too early to tell. We try to counsel our patients with these different options.

Join us to read the rest of Dr. Ost’s comments. (Subscribers can read the conversation in their March issue of Prostatepedia.)


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Dr. Piet Ost: Why Medicine?

Dr. Piet Ost is a radiation oncologist at Ghent University in Belgium. His work focuses on post-surgery radiation therapy and metastasis-directed therapy for oligometastatic prostate cancer, or a cancer recurrence with three or fewer metastases.

Prostatepedia spoke with him about what drew him to medicine.

Why did you become a doctor?

Dr. Piet Ost: It was a bit by coincidence. I planned to be an airline pilot, but due to some medical issues with my eyes, I was not allowed to fly. I’ve always had a big interest in anything scientifically sound where you can start with science and build up from there. I found evidence-based medicine interesting from the beginning. So I started an alternate plan to become a doctor. I enrolled in medical school and became more interested in getting patients involved in the science, in applying evidence-based medicine. How can we do that? Where are the big gaps in science?

In medical school, I realized that there are so many unanswered questions that patients ask on a daily basis. You just have to tell them what we know now, but that there are many things that we still do not know or fully understand. That communication process has helped me a lot in talking to patients. They helped me grow in this process once I graduated.

Subscribe to read Dr. Ost’s comments on oligometastatic prostate cancer.


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Dr. Eric Rohren: Why Radiology?

Dr. Eric Rohren is the chair of the department of radiology at Baylor College of Medicine.

Prostatepedia spoke with him about the path that led him to radiology.

Subscribe to read Dr. Rohren’s comments on radium therapy + imaging.

Why did you become a doctor?

Dr. Eric Rohren: I actually tried my best not to become a doctor initially. My father was a doctor. I grew up in the shadow of the Mayo Clinic up in Minnesota. I knew I was interested in science, but for a long time, I thought I wanted to pursue a career as a research scientist and not a physician.

As I made my way through college and looked at what I really enjoyed and what a career would look like, I wanted to focus on patient care and do things that impacted people. I looked for a career that could combine the science that I enjoyed with the ability to directly interact with people, to hopefully make their lives better. I came full circle, landing back in a career in medicine.

How did you end up in radiology and nuclear medicine?

Dr. Rohren: That was also a little bit indirect. Most medical students aren’t introduced to radiology until very late in their medical training.

A lot of people make the decision to do medicine or surgery well ahead of time, but radiology is often a latecomer. Nuclear medicine is even more so. It’s a subspecialty of imaging, its own medical specialty, but it can also be considered a part of radiology. Medical students often make it through their entire medical training without learning about nuclear medicine at all.

I was fortunate to have a mentor in the radiology department at the Mayo Clinic who taught me what he loved about radiology and how impactful it was on patient care. He got me further plugged in to nuclear medicine.

As I went into my residency and pursued it further, I decided that the science that I loved and the ability to do new things were most focused in radiology, and particularly in nuclear medicine. That’s the career I ended up with.

Many people assume radiology is just imaging. Is that the case? Where does it branch off into nuclear medicine? What kinds of therapies would a radiologist administer?

Dr. Rohren: A big part of being a radiologist is reading images. We also oversee the acquiring of the images, so we monitor the acquisition of the scans and the technologist performing the scans. Many of the people reading this article will have had X-rays, CTs, and MRIs. While technologists and nurses take them into the scanner and get them positioned, ultimately, the radiologists are the ones who oversee the program and make sure that the scans are acquired in the right way. They’re responsible for patient safety, the patient’s experience, and things like that.

At the back end, once the scan is complete, radiologists interpret the scans and look for the findings that may be used to guide medical decisions. Whereas many radiologists can go through their day and not see a patient, they do see the patient’s images. However, there are components of radiology that are directly related to therapy and directly patient-facing.

In interventional radiology, we do biopsies and endovascular procedures, catheter-based procedures, embolizations, administering treatment, and things like that. In women’s imaging such as mammography and breast cancer screenings, those radiologists spend a lot of their time talking to patients and counseling them about their diagnosis and procedures.

One area of radiology where we do meet with a patient face-to-face and interview or talk with them is in nuclear medicine. In that role, we act as “real doctors,” where we walk in, interview the patient, review their labs, go over the plan, do a consent process if it’s for a therapy that has some risks associated with it, and then we administer the therapy directly there in the clinic. When I serve in that role, I feel much more like a patient-facing physician than I do a traditional radiologist. It’s one of the most enjoyable things about it for me.

People tend not to be familiar with specialists until they need them. They might not really understand what you do until they’re at the point where they need your services.

Dr. Rohren: Generally, that is the impression, that the radiologist sits in a dark room, reads scans, and that’s the end of it. The national societies for radiology really encourage us to interface with patients and physicians to make our presence known. Radiologists need to do a better job of that. We have a critical role to play in the management of patients and the diseases that they’re dealing with, so the more we can be out there, share our professional knowledge, act as consultants, and act as physicians for the patients, that’s a positive thing.

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Advanced Imaging + Prostate Cancer

Dr. Phillip Koo is Division Chief of Diagnostic Imaging at the Banner MD Anderson Cancer Center.

Prostatepedia spoke with him about advanced imaging + recurrent prostate cancer.

Not a member? Join us to read more about recurrent prostate cancer.

Do you have any advice for men considering advanced imaging for prostate cancer?

Dr. Koo: We’ve been talking about better imaging tools for prostate cancer for years. When it comes to other cancers, we moved forward a great deal when FDG PET/CT became available. With prostate cancer, we’ve been stuck with CT and bone scans since the 1970s. They’re great tools. I don’t want to devalue what they’ve done for our patients since then, but we knew we could do better. Urologists and oncologists knew patients had metastatic disease, but our imaging tools limited detection.

We have new tools available to us in 2018. There is no question that costs are going to be higher, but that shouldn’t stop us from exploring and pushing the envelope. The whole purpose is to improve overall survival and treatment for our patients. An ounce of diagnosis could be a pound of cure. If we could identify disease sooner, identify the right patient for these exams, and use them at the right time, then we could probably create treatment plans more appropriate for patients with better outcomes. It’s something that I firmly believe. There is so much potential here.

When radiology is practiced in a vacuum, it’s not as powerful as when it’s integrated into patient histories and treatment plans. Radiology is a very powerful tool. But we often think of it as a commodity, something that does not have any distinguishing value. That is a huge under-estimation of radiology.

When performed correctly in a multidisciplinary setting, with access to the medical record and physicians who are taking care of the patient, radiology unlocks information that can really impact care for patients with prostate cancer. And we are currently only scratching the surface. This will change as analytic tools continue to analyze bigger data sets that include imaging and clinical data. If a urologist determines that their patient needs imaging, they’re going to write a request for imaging that describes what type of test they want and why they need it.

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Patients often go to the closest facility. Convenience is important, but when it comes to certain tests or exams, I urge patients to seek out subspecialized radiology experts and facilities with the experience and expertise in the performance and


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Imaging + Prostate Cancer Recurrence

Dr. Phillip Koo is Division Chief of Diagnostic Imaging at the Banner MD Anderson Cancer Center.

Prostatepedia spoke with him about imaging recurrent prostate cancer.

Not a member? Join us to read more about recurrent prostate cancer.

Prostatepedi:Some imaging occurs when men are first diagnosed. When, after treatment, do they encounter these newer imaging techniques? After a high PSA reading? Or just a part of routine follow-up?

Dr. Philip Koo: That’s a really tough question because imaging has a role throughout the continuum of care for any prostate cancer patient. Screening currently isn’t done with imaging, but there are a lot of research studies looking at it.

Prostate MRI is most often used for the detection of local disease. Oftentimes, patients with a rising PSA and a negative standard biopsy might get an MRI or an MRI-guided biopsy.

Bone scans and CT scans are used to help detect metastatic disease. There are many different scenarios, but usually after patients are diagnosed with cancer, most will visit radiology if there is a suspicion for metastatic disease. If we refer back to the RADAR 1 paper published in 2014 by Dr. Dave Crawford in Urology (see Urology 2014 Mar; 83(3): 664-9), we talk about imaging patients at initial diagnosis and imaging those who are intermediate or high-risk. In those patients, we recommended a bone scan and a CT scan.

Patients who are biochemically recurrent may also be imaged. Again, MRI will often be used to look for locally recurrent disease. Bone scans and CT scans are used to look for metastatic disease.

What about some of the newer imaging techniques?

Dr. Koo: The newer techniques are exciting. In both the patient community and the scientific community, we’ve heard a lot about these tools over the past decade. They weren’t widely available, especially in the United States. These newer imaging tools are simply better, which is why there is so much excitement. They will pick up more sites of disease at lower PSA levels.

When we do detect sites of disease, they’re more specific. Our confidence that these sites are actually disease is higher than our confidence when we’re using traditional bone and CT scans. These tests perform at a higher level compared to standard imaging.

Another benefit to these new tools is that in one single exam, we’ll be able to detect soft tissue and bony disease.

How do these newer techniques change treatment? If you can pick up the disease at a lower PSA is that going to change how a doctor treats a man?

Dr. Koo: Yes. We will be able to detect disease sooner. Currently, these newer imaging techniques are used mostly in patients with biochemical recurrence. When a patient has biochemical recurrence and we see the PSA rise, our standard imaging techniques are often not good enough to detect metastatic disease. The problem is that the radiation oncologist or the urologist needs to decide how they want to treat the patient.

Using these newer tools, we can provide the urologist or radiation oncologist with better information about whether or not the disease has spread at the time of biochemical recurrence. If it has not, and the urologist can perform salvage cryotherapy or a radiation oncologist does salvage radiotherapy, we could potentially cure the patient.

Really?

Dr. Koo: You’re hitting the disease before it spreads, so theoretically yes. These newe imaging techniques do better, but we really need to prove why this is important and how this impacts care. The answers to these questions will solidify the utility and value of these imaging techniques for prostate cancer patients.

If a patient gets the Gallium-68 PSMA or Axumin scans will his local urologist or oncologist know what to do with that information?

Dr. Koo: Maybe. The problem is that all of this sounds great: we have a tool that can detect disease sooner, better, and more accurately. But then the more important question is what to do with that information and does it impact outcomes. If we don’t know, then what is the value of that imaging tool? We operate under the assumption that earlier detection is always better, but we’re learning that in a lot of diseases that is not always true.

We could be over-diagnosing and over-treating certain diseases. Whether it’s imaging, urology, radiation oncology, or oncology, it really is a team effort because we all bring something unique to the table. We really need to work together to make sure we come up with the best plan and the best answers.

Join us to read the rest of Dr. Koo’s comments on imaging recurrent prostate cancer.


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Dr. Philip Koo: Why Medicine?

Koo-WEBDr. Phillip Koo is Division Chief of Diagnostic Imaging at the Banner MD Anderson Cancer Center.

Prostatepedia spoke with him about imaging recurrent prostate cancer. But first we asked him why he became a doctor.

Dr. Philip Koo: I became a doctor in large part because I couldn’t imagine anything better than spending my life learning about the human body and using that knowledge to improve human health. Given that I tended to do better in science and math, medicine provided a nice fit.

Why radiology?

Dr. Koo: During medical school rotations, you try a variety of specialties. A common theme in all my rotations was the central value or importance of imaging within the care of a patient. That piqued my interest in radiology. When I learned about radiology, I was captivated by looking at images or different techniques to capture a certain body process anatomically or physiologically and by being able to use that information combined with the clinical scenario in order to come up with a diagnosis.

Did you ever study engineering? I’ve been reading a lot about how radiology and imaging are becoming incorporated into the tech world, such as with IBM Watson.

Dr. Koo: I’m not much of a techie. Before I switched to one of those flat screens, my friends used to joke that I was the last person in the United States to have a tube TV.

To me, it’s not necessarily a disconnect with radiology because radiology is the practice of medicine. It is an art. No matter how much technology we implement, there still is an art to the way you practice the science of radiology.

There is no question that technology has caused a tremendous growth in our field over the past 10 to 20 years. These technologies were disruptive and beneficial to our specialty. Artificial intelligence and machine learning are the newest technologies poised to disrupt the specialty. As a specialty, we are embracing these tools and finding ways that they can be utilized to improve patient care.

Join us to read Dr. Koo’s comments on imaging + prostate cancer.